Simultaneous measurement of myocardial oxygen consumption and blood flow using [1-carbon-11]acetate.
[1-Carbon-11]acetate has been used as a tracer for oxidative metabolism with PET. The aim of this study was to validate, in humans, a previously proposed two-compartment model for [1-11C]acetate for the noninvasive measurement of myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF) with PET.


METHODS
Twelve healthy volunteers were studied with [13N]ammonia, [1-11C]acetate and PET. Myocardial oxygen consumption was invasively determined by the Fick method from arterial and coronary sinus O2 concentrations and from MBF obtained by [13N]ammonia PET.


RESULTS
Directly measured MVO2 ranged from 5.2 to 11.1 ml/100g/min, and MBF ranged from 0.48 to 0.88 ml/g/min. Oxidative flux through the tricarboxylic acid cycle, reflected by the rate constant k2, which correlated linearly with measured MVO2 [k2 = 0.0071 + 0.0074(MVO2); r = 0.74, s.e.e. = 0.015]. With this correlation, MVO2 could be estimated from the model-derived k2 value by MVO2 = 135(k2) - 0.96. The slope of this relationship was close to that previously obtained in rats and implies that the tricarboxylic acid cycle intermediate metabolite pool sizes are comparable. The net extraction (K1) of [1-11C]acetate, measured by PET, from blood into myocardium correlated closely with MBF by K1 = 0.15 + 0.73(MBF) (r = 0.93, s.e.e. = 0.033) and, thus, provided noninvasively obtainable measures of blood flow.


CONCLUSIONS
The proposed compartment model for [1-11C]acetate fits the measured kinetics well and, with proper calibration, allows estimation of absolute MVO2 rather than only an index of oxidative metabolism. Furthermore, [1-11C]acetate-derived estimates of MBF are feasible.
Sun
K T
KT
Department of Molecular and Medical Pharmacology, School of Medicine, University of California, Los Angeles 90095-1735, USA.
Yeatman
L A
LA
Buxton
D B
DB
Chen
K
K
Johnson
J A
JA
Huang
S C
SC
Kofoed
K F
KF
Weismueller
S
S
Czernin
J
J
Phelps
M E
ME
Schelbert
H R
HR
D019342:Acetic Acid; D000641:Ammonia; D001794:Blood Pressure; D002250:Carbon Radioisotopes; D003326:Coronary Circulation; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009590:Nitrogen Radioisotopes; D010101:Oxygen Consumption; D019275:Radiopharmaceuticals; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D009590:Nitrogen Radioisotopes; D019275:Radiopharmaceuticals; D000641:Ammonia; D019342:Acetic Acid